Design and Application of Intelligent Local Anesthetic Nanoformulations.

Local analgesia is a prevalent and cost-effective pain management strategy with minimal systemic side effects. At the same time, nanotechnology has been employed to achieve the sustained release of drugs to prolong the duration of local anesthetics (LAs). However, these traditional nanoformulations lack responsiveness and thus cannot achieve precise pain relief through on-demand administration. The emergence of "intelligent" nanosystems with stimulus-response capabilities has opened up new prospects in pain control. This review summarizes recent advancements in the design and application of triggerable LAs nanoformulations that can be activated by external stimuli such as light, ultrasound, or heat. These systems facilitate precise, patient-specific pain management, transforming the clinical approach from long-term suppression to controllable and on-demand relief. Finally, we discussed the current challenges and future prospects. A deeper understanding of this field will facilitate the development of superior analgesic solutions and ultimately improve the treatment outcomes for patients.